Pharmaceutisch Weekblad

, Volume 7, Issue 6, pp 252–259 | Cite as

Determination of sulfinpyrazone and four metabolites in plasma and urine by high pressure liquid chromatography

  • E. G. W. M. Lentjes
  • Y. Tan
  • C. A. M. Van Ginneken
Original Articles


An HPLC method for the simultaneous determination of sulfinpyrazone and itsp-hydroxy, sulfone, sulfide andp-hydroxysulfide metabolites in human plasma and urine samples was developed. Optimization with regard to sample preparation and chromatographic conditions was investigated. In the final procedure samples were acidified with HCl, extracted with a 1+1 (vol/vol) mixture of 1-chlorobutane and chloroform; urine extracts were re-extracted with citrate buffer (pH 4.5). HPLC was performed on reversed phase (RP 8) columns with a 48+52 (vol/vol) mixture of ethanol and citrate buffer (pH 2.5) as the mobile phase. The lower limit of detection for sulfinpyrazone and the sulfide metabolite is 10 ng/ml, for the other metabolites it is 50 ng/ml. An example of application of this procedure to pharmacokinetic studies in a volunteer receiving a single oral dose of sulfinpyrazone is given.


Sulfide Urine Sample Oral Dose Human Plasma Reversed Phase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Burns JJ, Yü TF, Ritterband A, Perel JM, Gutman AB, Brodie BB. A potent new uricosuric agent, the sulfoxide metabolite of the phenylbutazone analogue G-25671. J Pharmacol Exp Ther 1957;119:418–26.PubMedGoogle Scholar
  2. 2.
    Pfister B, Imhof P, Wirz H. Effect of sulphinpyrazone (Anturan®) on uric acid excretion and plasma uric acid concentration in healthy volunteers. Eur J Clin Pharmacol 1978;13:263–5.PubMedGoogle Scholar
  3. 3.
    Smythe HA, Ogryzlo MA, Murphy EA, Mustard JF. The effect of sulfinpyrazone (Anturan®) on platelet economy and blood coagulation in man. Can Med Assoc J 1965;92:818–21.PubMedGoogle Scholar
  4. 4.
    Margulies EH, White AM, Sherry S. Sulfinpyrazone: a review of its pharmacological properties and therapeutic use. Drugs 1980;20:179–97.PubMedGoogle Scholar
  5. 5.
    Anturane Reinfarction Trial Research Group. Sulfinpyrazone in the prevention of cardiac death after myocardial infarction. N Engl J Med 1978;298:289–95.Google Scholar
  6. 6.
    Anturane Reinfarction Trial Research Group. Sulfinpyrazone in the prevention of sudden death after myocardial infarction. N Engl J Med 1980;302:250–6.Google Scholar
  7. 7.
    Anturan Reinfarction Italian Study. Sulfinpyrazone in post-myocardial infarction. Lancet 1982;1:237–42.Google Scholar
  8. 8.
    Misra NP, Bhargava RK, Manoria PC, Dutta S, Nema V. Comparative trial of sulphinpyrazone and aspirin + dipyridamole in acute myocardial infarction. Curr Ther Res 1983;34:558–66.Google Scholar
  9. 9.
    Kolata GB. FDA says no to Anturane. Science 1980;208:1130–2.PubMedGoogle Scholar
  10. 10.
    Temple R, Pledger GW. The FDA's critique of the Anturane Reinfarction Trial. N Engl J Med 1980;303:1488–92.PubMedGoogle Scholar
  11. 11.
    Anturane Reinfarction Trial Policy Committee. The Anturane Reinfarction Trial: reevaluation of outcome. N Engl J Med 1982;306:1005–8.Google Scholar
  12. 12.
    Kaegi A, Pineo GF, Shimizu A, Trivedi H, Hirsh J, Gent M. Arteriovenous-shunt thrombosis — prevention by sulfinpyrazone. N Engl J Med 1974;290:304–6.PubMedGoogle Scholar
  13. 13.
    Bern MM, Cavaliere BM, Lukas G. Plasma levels and effects of sulfinpyrazone in patients requiring chronic haemodialysis. J Clin Pharmacol 1980;20:107–16.PubMedGoogle Scholar
  14. 14.
    Evans G, Gent M. Effects of platelet suppressive drugs on arterial and venous thromboembolism. In: Hirsch J, Cade JF, Gallus AS, Schönbaum E, eds. Platelets, drugs and thrombosis. Basel: S. Karger, 1975:258–62.Google Scholar
  15. 15.
    Canadian Cooperative Study Group. A randomized trial of aspirin and sulfinpyrazone in threatened stroke. N Engl J Med 1978;299:53–9.Google Scholar
  16. 16.
    Ali M, McDonald JWD. Effects of sulfinpyrazone on prostaglandin synthesis and platelet release of serotonin. J Lab Clin Med 1977;89:868–75.PubMedGoogle Scholar
  17. 17.
    Moschos CB, Escobinas AJ, Jorgensen OB, Regan TJ. Effect of sulfinpyrazone on ventricular fibrillation during acute myocardial ischemia. Circulation 1981;64:13–8.PubMedGoogle Scholar
  18. 18.
    Beamish RE, Dhillon KS, Singal PK, Dhalla NS. Protective effect of sulfinpyrazone against catecholamine metabolite adrenochrome induced arrhythmics. Am Heart J 1981;102:149–52.PubMedGoogle Scholar
  19. 19.
    Wilcox RG, Richardson D, Hampton JR, Mitchell JRA, Banks DC. Sulphinpyrazone in acute myocardial infarction: studies on cardiac rhythm and renal function. Br Med J 1980;281:531–4.PubMedGoogle Scholar
  20. 20.
    Buchanan MR, Rosenfeld J, Hirsh J. The prolonged effect of sulfinpyrazone on collagen-induced platelet aggregationin vivo. Thromb Res 1978;13:883–92.PubMedGoogle Scholar
  21. 21.
    Butler KD, Wallis RB, White AM. A study of the relationship betweenex vivo andin vivo effects of sulphinpyrazone in the Guinea Pig. Haemostasis 1979;8:353–60.PubMedGoogle Scholar
  22. 22.
    Maguire ED, Pay GF, Turney J. et al. The effect of two different dosage regimens of sulphinpyrazone on platelet functionex vivo and blood chemistry in man. Haemostasis 1981;10:153–64.PubMedGoogle Scholar
  23. 23.
    Kirstein-Pedersen A, Jakobsen P. Two new metabolites of sulphinpyrazone in the rabbit: a possible cause of the prolongedin vivo effect. Thromb Res 1979;16:871–6.PubMedGoogle Scholar
  24. 24.
    Kirstein-Pedersen A, Jakobsen P. Sulphinpyrazone metabolism during long-term therapy. Br J Clin Pharmacol 1981;11:597–603.PubMedGoogle Scholar
  25. 25.
    Pay GF, Wallis RB, Zelaschi D. The effect of sulphinpyrazone and its metabolites on platelet functionin vitro andex vivo. Haemostasis 1981;10:165–75.PubMedGoogle Scholar
  26. 26.
    Wallis RB. Mechanism of action of sulphinpyrazone. Thromb Res 1983;(suppl IV):31–8.Google Scholar
  27. 27.
    Dayton PG, Sicam LE, Landrau M, Burns JJ. Metabolism of sulfinpyrazone (Anturane) and other thio analogues of phenylbutazone in man. J Pharmacol Exp Ther 1961;132:287–90.PubMedGoogle Scholar
  28. 28.
    Inaba T, Besley ME, Chow EJ. Determination of sulfinpyrazone in serum by high-performance liquid chromatography. J Chromatogr 1975;104:165–9.PubMedGoogle Scholar
  29. 29.
    Dieterle W, Faigle JW, Mory H, Richter WJ, Theobald W. Biotransformation and pharmacokinetics of sulfinpyrazone (Anturan®) in man. Eur J Clin Pharmacol 1975;9:135–45.PubMedGoogle Scholar
  30. 30.
    Lecaillon JB, Souppart C. Quantitative assay of sulphinpyrazone in plasma and urine by high-performance liquid chromatography. J Chromatogr 1976;121:227–34.PubMedGoogle Scholar
  31. 31.
    Rosenfeld J, Buchanan M, Powers P, Hirsh J, Barnett HJM, Stuart RK. Determination of sulphinpyrazone in patient plasma by gas chromatography. Thromb Res 1978;12:247–55.PubMedGoogle Scholar
  32. 32.
    Wong LT, Solomonraj G, Thomas BH. Simple and rapid micro-determination of sulfinpyrazone (Anturan) in biological fluids by reversed-phase high-performance liquid chromatography. J Chromatogr 1978;150:521–6.PubMedGoogle Scholar
  33. 33.
    Jakobsen P, Kirstein-Pedersen A. Determination of sulfinpyrazone and two of its metabolites in human plasma and urine by gas chromatography and selective detection. J Chromatogr 1979;163:259–69.PubMedGoogle Scholar
  34. 34.
    Bjornsson TD, Wolfram KM, Routledge PA, Shand DG. High-Performance Liquid Chromatographic analysis of sulfinpyrazone and its metabolites in biological fluids. J Chromatogr 1980;181:417–25.PubMedGoogle Scholar
  35. 35.
    Dieterle W, Faigle JW, Moppert J. New metabolites of sulfinpyrazone in man. Arzneim Forsch/Drug Res 1980;30:989–93.Google Scholar
  36. 36.
    Jakobsen P, Kirstein-Pedersen A. Two metabolites of sulphinpyrazone and their identification and determination by mass spectrometry. J Pharm Pharmacol 1981;33:89–92.PubMedGoogle Scholar
  37. 37.
    Jakobsen P, Kirstein-Pedersen A. Simultaneous determination of sulfinpyrazone and four of its metabolites by high-performance liquid chromatography. J Chromatogr 1981;223:460–5.PubMedGoogle Scholar
  38. 38.
    Bradbrook ID, John VA, Morrison PJ, Rogers HJ, Spector RG. Pharmacokinetics of single doses of sulphinpyrazone and its major metabolites in plasma and urine. Br J Clin Pharmacol 1982;13:177–85.PubMedGoogle Scholar
  39. 39.
    Godbillon J, Gauron S, Gosset G. High-performance liquid chromatographic analysis of the sulfide metabolite of sulfinpyrazone in man. J Chromatogr 1982;227:516–20.PubMedGoogle Scholar
  40. 40.
    Patel NJ, Kildsig DO, Banker GS, Mayer PR, Gonzalez MA. Paired-ion High-performance liquid chromatographic assay for sulfinpyrazone in plasma. J Pharm Sci 1982;71:1413–5.PubMedGoogle Scholar
  41. 41.
    De Vries JX, Staiger C, Wang NS, Schlicht F. Analysis of sulfinpyrazone and its metabolites in human plasma and urine by high-performance liquid chromatography. J Chromatogr 1983;277:408–13.PubMedGoogle Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1985

Authors and Affiliations

  • E. G. W. M. Lentjes
    • 1
  • Y. Tan
    • 1
  • C. A. M. Van Ginneken
    • 1
  1. 1.Department of PharmacologyCatholic University of NijmegenHB NijmegenThe Netherlands

Personalised recommendations